A stroke is a brain disease either by ischemia caused by a cerebral artery blockage or by hemorrhage when a blood vessel ruptures and bleeds into the brain. According to American Stroke Association (www.strokeassociation.org), strokes are currently the 4th cause of death and a 1st reason of disability in the United States. About 780,000 strokes occur annually in the US. Strokes have incurred tremendous impact and financial cost to our society. Projected cost is estimated to be about 2.2 trillion dollars by 2050 (Brown, et al., “Projected costs of ischemic stroke in the United States”, Neurology, 67(8):1390-1395 (2006)). It is imperative to have a more effective method to improve the treatment and prevention of the disease.
Early Alert is Critical for Stroke Treatment:
The key for effective stroke care is time from its onset to receiving medical treatment. The first line standard medicine against an ischemic stroke, which represents about 87% of all strokes, is a thrombolytic drug called tissue plasminogen activator (tPA) (Adams, et al., “Guidelines for the early management of adults with ischemic stroke”, Stroke, 38:1655-1711 (2007)). The tPA was approved by the FDA in 1996. It can dissolve the blood clot and restore the blood flow. The thrombolytic therapy can significantly reduce or reverse the effects of a stroke and prevent permanent disability. However, the tPA needs to be given to an ischemic stroke patient within 3 hours after the stroke's onset. After the 3 hour window, the drug is no longer effective and may increase the risk of bleeding inside the brain. In order to keep explanation concise, the description in this patent application focuses more on the ischemic stroke while the present invention can be applied to both ischemic and hemorrhagic strokes.
Hemorrhagic stroke, which stands for about 13% of all strokes, has a high mortality rate of ˜40%. While no medicine for the hemorrhagic stroke has the 3 hour limit, it still requires prompt treatment. Usually half of the deaths happen within the first 2 days (Joseph, et al., “Guidelines for the management of spontaneous intracerebral hemorrhage”, Stroke. 30:905-915 (1999)), (Bederson et al., “Guidelines for the management of aneurysmal subarachnoid hemorrhage”, Stroke, 40: 994-1025 (2009)). The disease is considered one of the highest degree medical emergencies. Early diagnosis and treatment are needed to reduce the mortality.
Unfortunately, “Generally, only 3 to 5 percent of those who suffer a stroke reach the hospital in time to be considered for this treatment” according to American Stroke Association (www.strokeassociation.org). About 95% of the ischemic stroke patients missed the thrombolytic therapy, which is the treatment of choice. Unlike heart attack symptoms which usually include severe chest pain, stroke symptoms vary much depending on where a stroke occurs in the brain. Severe strokes can have sudden numbness, vision change, imbalance, trouble in speaking or walking, headache etc. In other cases, the initial symptoms may be mild depending on which blood vessel inside the brain is blocked. The symptoms may be mistakenly considered as causes of other health conditions such as aging or sickness. Sometimes, a stroke patient may not be aware of any abnormality during sleep until wake-up. Many strokes are painless. All of these factors lead to a delay by a stroke patient to seek immediate medical diagnosis and the critical thrombolytic therapy. Early detection and alarm of a stroke's onset are pivotal for improving current stroke management.
Current standard technologies for stroke diagnosis are Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Ultrasound. These detections are accurate. However, they are expensive equipment. The procedures can only be done by a medical professional in a hospital or clinic. CT and MRI need specially shielded room. A potential stroke patient cannot be put under the continuous monitoring by the equipments. The three technologies are good for stroke diagnosis in hospital, but not appropriate for regular daily use at home or office for an early stroke alarm to help bring a stroke patient to a hospital for early medical treatment.
Therefore it is highly desirable to have an alarm device to automatically detect and promptly alert the onset of a stroke attack. The device needs to be continuously wearable because the time when a stroke starts is unknown. A potential stroke patient needs to be continuously monitored. The device shall have good accuracy and coverage of different stroke types. It is also desirable to be non-invasive and simple to operate. The alarm can be sent as an alert to the patient, a caregiver or medical professional to immediately seek further medical diagnosis by CT, MRI or ultrasound and treatment like tPA.
The stroke alerts, as that practiced by those of ordinary skill in the art, are not adequate and not able to effectively help fight against a stroke or save a life.
Several patented disclosures have tried to detect a stroke's onset by asking the patient to perform certain physical tasks related to stroke symptoms. For example, U.S. Pat. No. 2007/0021687 A1 instructed a patient to do strength measurements to make detection. U.S. Pat. No. 6,592,378 B2 asked the patient to answer several symptoms-related questions to decide whether a stroke has occurred. U.S. Pat. No. 2008/0294019 A1 uses chest movement, patient position and other vital signs as criteria for a stroke alert. All these methods are based on external physical symptoms of a stroke. However, they can only cover certain cases with obvious symptoms. The detections often lag well behind the start of a stroke attack. These methods may not work if a stroke happens during sleep. Most of the methods are not automatic and need a patient's involvement. These methods will lead to a delay for stroke treatment.
Another technique is based on monitoring the changes of a biochemical component or marker in the blood or other biological samples. For example, US 2010/0167322 A1 measures the aldehyde compounds. U.S. Pat. No. 7,427,490, B2 detects the presence of a certain chemical marker such as a B-type natriuretic peptide from a patient's blood sample. The technique is invasive and needs to take biological samples from a patient. These reasons make the technique inconvenient or improper for continuous monitoring.
Other known prior art includes electroencephalogram (EEG), brain wave, and impedance plethysmography (IPG) or photoplethysmography (PPG) on a patient's head such as US 2011/0245707 A1 and US 2011/0201950 A1. EEG and brain wave use multiple electrical nodes attached the head to detect the electrical functional activity of the brain. The methods are more sensitive for seizure, which involves high abnormity of electrical signaling in the brain. A stroke can be due to any big or small blood vessel. The effect on cerebral electrical signaling by a stroke may or may not be significant. As a result, EEG and brain wave may only cover a small percentage of stroke cases. IPG measures cerebral impedance change. PPG on head measures volumetric change of cerebral blood. Similar to the EEG, the IPG/PPG methods are sensitive to certain severe cerebral changes such as big vessel blockage and insensitive to deep or small vessel damages. As of now, no coverage information based on a large number of clinical stroke cases has been reported for these methods. Overall, these methods may have limited coverage of stroke cases. In addition, wearing a bulky device on head may not appeal to patients.
Because of the limits as described above, none of the prior arts has successfully brought a viable stroke alarm product to stroke patients so far. Potential stroke patients still live in constant fear of a possible stroke attack and worry about when a stroke will come and how to prepare for the attack.
Thus a new method and device are needed to alarm a stroke's onset. The device shall be continuously wearable, non-invasive, simple to operate and with good accuracy and coverage of different stroke types. The invention of the current patent presents such a device to a stroke patient. The present patent is based on extensive research and analysis on the clinical evidences and data about stroke and blood pressure as summarized in Paragraph [0015-0018].
It has been known for years that the blood pressure (BP) spontaneously changes in most stroke patients (Wallace, et al., “Blood pressure after stroke”, JAMA 246(19): 2177-2180 (1981)). In a study involved in 563,704 stroke patients presenting to the emergency departments, 69% showed elevated blood pressure at the time of admission (Qureshi, et al., “Prevalence of Elevated Blood Pressure in 563,704 Adult Patients Presenting to the Emergency Department with Stroke in the United States”, Am J Emerg Med, 25(1): 32-38 (2007)). In another study by the International Stroke Trial from 467 hospitals in 36 countries, ˜82% of 17,398 patients had high blood pressure based on the WHO definition of hypertension (systolic BP>140 mm Hg) within the first 48 hours following acute stroke (Leonardi-Bee, et al., “Blood pressure and clinical outcomes in the International Stroke Trial”, Stroke. 33: 1315-1320 (2002)). Some of the stroke patients did not have prior history of hypertension. Some of the patients had hypertension before (Rodriguez-Yanez, et al., “New-onset hypertension and inflammatory response/poor outcome in acute ischemic stroke”, Neurology, vol. 67, no. 11: 1973-1978 (2006)). Other research studied the prognostic significance of the initial blood pressure change (Aslanyan, et al. “Effect of blood pressure during the acute period of ischemic stroke on stroke outcome: a tertiary analysis of the GAIN International Trial”, Stroke, 34(10): 2420-2425 (2003)); (Rodriguez-Garcia J L, et al. “Significance of elevated blood pressure and its management on the short-term outcome of patients with acute ischemic stroke”, Am J Hypertens 18(3):379-384 (2005)). The BP pattern change is believed to be a natural compensatory auto-regulation mechanism to maintain cerebral blood flow and reduce neuronal death while the presence of the ultra high blood pressure for an extended time may incur damage as well (Yong, et al., “Characteristics of blood pressure profiles as predictors of long-term outcome after acute ischemic stroke”, Stroke, 36:2619-2625 (2005)).
On the other hand, BP is also known for its intrinsic fluctuation and instability for decades since a BP measurement technique became available. BP is not constant even for a normal healthy person. When BP is measured at different times for the same person, the measured BP values may be different. BP may go up and down multiple times within a day (Millar Craig, et al., “Circadian Variation of Blood-Pressure”, The Lancet, April 15: 795-797 (1978)). BP is also affected by the person's mood, motion, food, drug etc (Räikkönen, et al., “Effects of hostility on ambulatory blood pressure and mood during daily living in healthy adults”, Health Psychology, Vol 18(1), 44-53 (1999)) (James, et al., “The influence of happiness, anger and anxiety on the blood pressure of borderline hypertensives”, Psychosomatic Medicine Vol. 48, No. 7 (1986)). BP is believed to be continuously changing naturally. The general perception of the normal BP variations and lack of a continuous BP measurement technology may have prevented proposing use of BP change for stroke detection.
The present patent did a further research and analysis about the detail characteristics of BP and finds that the BP pattern after a stroke's onset is different from that of normal BP fluctuations as described in Paragraph [0016]. The BP after a stroke's onset showed different dynamic and pattern. The BP change in a stroke event is usually within about half hour and takes about hours to days to fall back to the pre-stroke level (Broderick, et al., “Blood pressure during the first minutes of focal cerebral ischemia”, Ann Emerg Med., 22(9):1438-43 (1993)), (Ntaios, et al., “Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment”, Journal of Hypertension, Vol 29 (8): 1583-1589 (2011)), (Semplicini, et al., “Hypertension in acute ischemic stroke: A compensatory mechanism or an additional damaging factor?”, Arch Intern Med, vol 167: 211-216 (2003)). However, the normal BP changes but stays around the baseline (Gardner, et al., “24-Hour Ambulatory Blood Pressure Monitoring in Primary Care”, JABFP, Vol 14, No 3: 166-171 (2001)). If the patient does not have history of hypertension, the BP will normally stay below the hypertension zone, <140 mmHg for systolic BP. If the patient has prior hypertension, the BP will stay around the patient's base level (Khoury, et al., “Ambulatory blood pressure monitoring in a nonacademic setting. Effects of age and sex”, Am J Hypertension, 5(9):616-23 (1992)). When there is a change, the change tends to be short and quickly returns to the base curve and trend.
After studying a large amount of clinical data and evidences about BP and stroke as summarized above, the present patent concludes that the BP pattern after a stroke's onset is distinguishable from the patient's normal BP fluctuation pattern. The current patent further proposes to continuously monitor BP or a BP-related hemodynamic parameter for detecting a stroke's onset. However, currently there is no effective method and apparatus in the field of medical device industries to continuously monitor the blood pressure and set a stroke alarm that can be carried out conveniently and comfortably for a long time. A stroke occurs unexpectedly. The monitoring device needs to be continuously wearable for days, weeks, years or even a patient's whole life.
Current BP measurement technologies do not fit the requirements for noninvasive continuous wearing for detecting a stroke's onset. They are for a short term test, not for a long term use. The BP measurement methods on market include invasive vascular pressure monitoring, sphygmomanometer and oscillometry. The invasive vascular pressure method involves placing a cannula needle or catheter into an artery. This method is most accurate. However, apparently it is not proper for continuous everyday wearing. Sphygmomanometer uses a stethoscope and a cuff to do the measurement based on Korotkoff sounds. Oscillometry uses a cuff and electronics to decide the blood pressure based on cuff pressure oscillations. Both sphygmomanometer and oscillometry need to inflate and deflate the burdensome cuff, which interrupts regular sleep and activities. The methods can measure blood pressure but they are cumbersome and uncomfortable. They cannot be used for continuous ambulatory BP measurement for a long time. A patient cannot wear them on a regular daily bases. So these BP measurement technologies are not suitable for use for a stroke alert, which requires monitoring the BP change continuously.
For these reasons, in addition to using BP as the basis for stroke detection and alert, it is also required to have a new technical approach. In order to overcome the above difficulties and problems, the apparatus must be continuously wearable, uses no cuff and does not require complex procedures to operate. The invention in the current patent presents such a new method and apparatus for a stroke onset alarm by further proposing to utilize and analyze another hemodynamic parameter, pulse transit time (PTT). The pulse transit time is the time for an arterial pulse wave to propagate between two different arterial sites. PTT is another characteristic parameter of blood circulation and related to BP (Paragraph [0047]). The above clinical observation (Paragraph [0015-0018]) about the relationship between a stroke's onset and BP change can be extrapolated to the relationship between the stroke's onset and PTT change. More importantly, unlike the BP measurement technologies, the method and apparatus in the present patent for monitoring and analyzing PTT to identify and detect a stroke's onset fit the requirements for long term use for a stroke alert such that the aforementioned difficulties and problems can be overcome.